Patients undergoing allogeneic bone marrow transplantation who are seropositive for cytomegalovirus are vulnerable to serious cytomegalovirus infection, presumably because of reactivation of latent endogenous virus and severe immunosuppression. We administered intravenous acyclovir from 5 days before to 30 days after allogeneic marrow transplantation for hematologic neoplasms in an effort to prevent cytomegalovirus infection and disease in patients seropositive for cytomegalovirus before transplantation. Eighty-six patients seropositive for both cytomegalovirus and herpes simplex virus before transplantation received acyclovir, whereas 65 patients seropositive only for cytomegalovirus served as controls (acyclovir is the standard prophylactic agent against herpes simplex virus in this setting). The probability that cytomegalovirus infection would develop within the first 100 days after transplantation was 0.70 among acyclovir recipients and 0.87 among control patients at medians of 62 and 40 days after transplantation, respectively (P = 0.0001 by log-rank test). Invasive cytomegalovirus disease developed in 19 acyclovir recipients (22 percent) and 25 control patients (38 percent) (P = 0.008). Survival within the first 100 days after transplantation was better among acyclovir recipients (P = 0.002). Acyclovir prophylaxis was associated with a relative risk of 0.5 or less for the development of cytomegalovirus infection or disease or for death within the first 100 days after transplantation (P less than or equal to 0.04), in proportional-hazards regression analysis. We conclude that prophylaxis with intravenous acyclovir significantly reduced the risk of both cytomegalovirus infection and cytomegalovirus disease in seropositive patients after allogeneic bone marrow transplantation and that it was also associated with significantly improved survival.
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Fred Hutchinson Cancer Research Center, Program in Infectious Diseases, Seattle, WA 98104.
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Griffiths, P. D.
(2002). The treatment of cytomegalovirus infection. J Antimicrob Chemother
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[Abstract][Full Text]
Szmania, S., Galloway, A., Bruorton, M., Musk, P., Aubert, G., Arthur, A., Pyle, H., Hensel, N., Ta, N., Lamb, L. Jr, Dodi, T., Madrigal, A., Barrett, J., Henslee-Downey, J., van Rhee, F.
(2001). Isolation and expansion of cytomegalovirus-specific cytotoxic T lymphocytes to clinical scale from a single blood draw using dendritic cells and HLA-tetramers. Blood
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[Abstract][Full Text]
(2000). Management of herpes virus infections following transplantation. J Antimicrob Chemother
45: 729-748
[Full Text]
Talarico, C. L., Burnette, T. C., Miller, W. H., Smith, S. L., Davis, M. G., Stanat, S. C., Ng, T. I., He, Z., Coen, D. M., Roizman, B., Biron, K. K.
(1999). Acyclovir Is Phosphorylated by the Human Cytomegalovirus UL97 Protein. Antimicrob. Agents Chemother.
43: 1941-1946
[Abstract][Full Text]
Guinan, E. C., Boussiotis, V. A., Neuberg, D., Brennan, L. L., Hirano, N., Nadler, L. M., Gribben, J. G.
(1999). Transplantation of Anergic Histoincompatible Bone Marrow Allografts. NEJM
340: 1704-1714
[Abstract][Full Text]
Diamond, D. J., York, J., Sun, J.-Y., Wright, C. L., Forman, S. J.
(1997). Development of a Candidate HLA A*0201 Restricted Peptide-Based Vaccine Against Human Cytomegalovirus Infection. Blood
90: 1751-1767
[Abstract][Full Text]
Reusser, P., Attenhofer, R., Hebart, H., Helg, C., Chapuis, B., Einsele, H.
(1997). Cytomegalovirus-Specific T-Cell Immunity in Recipients of Autologous Peripheral Blood Stem Cell or Bone Marrow Transplants. Blood
89: 3873-3879
[Abstract][Full Text]
Armitage, J. O.
(1994). Bone Marrow Transplantation. NEJM
330: 827-838
[Full Text]
Pizzo, P. A.
(1993). Management of Fever in Patients with Cancer and Treatment-Induced Neutropenia. NEJM
328: 1323-1332
[Full Text]
Shelhamer, J. H., Toews, G. B., Masur, H., Suffredini, A. F., Pizzo, P. A., Walsh, T. J., Henderson, D. K.
(1992). Respiratory Disease in the Immunosuppressed Patient. ANN INTERN MED
117: 415-431
[Abstract]
Bortin, M. M., Horowitz, M. M., Gale, R. P., Barrett, A. J., Champlin, R. E., Dicke, K. A., Gluckman, E., Kolb, H.-J., Marmont, A. M., Mrsic, M., Sobocinski, K. A., Weiner, R. S., Rimm, A. A.
(1992). Changing Trends in Allogeneic Bone Marrow Transplantation for Leukemia in the 1980s. JAMA
268: 607-612
[Abstract]
Stratta, R. J., Shaefer, M. S., Cushing, K. A., Markin, R. S., Reed, E. C., Langnas, A. N., Pillen, T. J., Shaw, B. W. Jr
(1992). A Randomized Prospective Trial of Acyclovir and Immune Globulin Prophylaxis in Liver Transplant Recipients Receiving OKT3 Therapy. Arch Surg
127: 55-64
[Abstract]
Sayers, M. H., Anderson, K. C., Goodnough, L. T., Kurtz, S. R., Lane, T. A., Pisciotto, P., Silberstein, L. E.
(1992). Reducing the Risk for Transfusion-transmitted Cytomegalovirus Infection. ANN INTERN MED
116: 55-62
[Abstract]
Marchbanks, C. R., Rowley, K. A.
(1991). Update on Infections in the Immunocompromised Host. Journal of Pharmacy Practice
4: 282-294
[Abstract]
King, S. M., Petric, M., Superina, R., Graham, N., Roberts, E. A.
(1990). Cytomegalovirus Infections in Pediatric Liver Transplantation. Arch Pediatr Adolesc Med
144: 1307-1310
[Abstract]
Stratta, R. J., Shaefer, M. S., Markin, R. S., Wood, R. P., Kennedy, E. M., Langnas, A. N., Reed, E. C., Woods, G. L., Donovan, J. P., Pillen, T. J., Duckworth, R. M., Shaw, B. W. Jr
(1989). Clinical Patterns of Cytomegalovirus Disease After Liver Transplantation. Arch Surg
124: 1443-1450
[Abstract]
Balfour, H. H. Jr, Englund, J. A.
(1989). Antiviral Drugs in Pediatrics. Arch Pediatr Adolesc Med
143: 1307-1316
[Abstract]